Tiotropium

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

Tiotropium is an inhaled long-acting, antimuscarinic agent for the treatment of chronic obstructive pulmonary disease (COPD). It inhibits the M3-receptors of the airway smooth muscle leading to bronchodilation. Although mostly excreted unchanged it may in some part be metabolized by CYP2D6 and CYP3A4.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Tiotropium.

Excerpt from the Tiotropium (Spiriva) drug label:
"In vitro experiments with human liver microsomes and human hepatocytes suggest that a fraction of the administered dose (74% of an intravenous dose is excreted unchanged in the urine, leaving 25% for metabolism) is metabolized by cytochrome P450-dependent oxidation and subsequent glutathione conjugation to a variety of Phase II metabolites. This enzymatic pathway can be inhibited by CYP450 2D6 and 3A4 inhibitors, such as quinidine, ketoconazole, and gestodene. Thus, CYP450 2D6 and 3A4 are involved in the metabolic pathway that is responsible for the elimination of a small part of the administered dose. In vitro studies using human liver microsomes showed that tiotropium in supra-therapeutic concentrations did not inhibit CYP450 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1, or 3A4."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Tiotropium (Spiriva) drug label PDF.